In many of the developing countries of the world, schistosomiasis, fascioliasis, and other snail-borne parasites continue to impose an intolerable burden of human suffering, and of diminished productivity of domestic animals. The long term goal of the proposed research is to better understand the complex and evolutionarily ancient associations between larval flukes and their snail hosts. By learning how larval trematodes evade or suppress the internal defense systems of their molluscan hosts, the changes of successfully mitigating the impact of such parasites through implementation of rational control measures are increased. The available evidence suggests that larvae of some, and perhaps all, trematode species actively suppress the snail's immune system, a phenomenon termed interference (Lie 1982). Recent work implies that hemocytes, the circulating immune cells of snails, are the targets of interference, and indirect evidence suggests that the effect can be mediated by soluble factors released from trematode larvae. Using the trematode Echinostoma paraennsei and the snail Biomphalaria glabrata as a model system, the proposed research seeks to define more precisely the effects of infection on hemocytes, and to provide more direct evidence for the role of trematode secretory/excretory products (SEP) in mediating interference. E. paraensei has several advantageous properties for such a study: its suppressive effects are known to be strong, its larvae can be easily collected in large numbers, and its in vivo development can be unobtrusively studied. Lectins and anti-hemocyte or anti-SEP antibodies will be used as probes to assess alterations in hemocyte surfaces resulting from infection. Also, E. paraensei larvae will be cultured in vitro, and their SEP will be collected, and characterized using SDS-PAGE electrophoresis. SEP will be injected into snails to learn if SEP can mimic the effects of infection, or alter the snail's resistance to infection with E. paraensei or Schistosoma mansoni. Anti-SEP will be used in conjunction with immunoblotting to determine if SEP binds to hemocytes. The proteolytic and anti-proteolytic effects of SEP will be assessed. This research will more precisely define the manner in which trematode suppression is mediated, and will set the stage for isolation and characterization of specific components of SEP with biological relevance.